title: EC-SPE-stripline-NMR analysis of reactive products: a feasibility study.
abstract: Flow-through electrochemical conversion (EC) of drug-like molecules was hyphenated to miniaturized nuclear magnetic resonance spectroscopy (NMR) via on-line solid-phase extraction (SPE). After EC of the prominent p38α mitogen-activated protein kinase inhibitor BIRB796 into its reactive products, the SPE step provided preconcentration of the EC products and solvent exchange for NMR analysis. The acquisition of NMR spectra of the mass-limited samples was achieved in a stripline probe with a detection volume of 150 nL offering superior mass sensitivity. This hyphenated EC-SPE-stripline-NMR setup enabled the detection of the reactive products using only minute amounts of substrate. Furthermore, the integration of conversion and detection into one flow setup counteracts incorrect assessments caused by the degradation of reactive products. However, apparent interferences of the NMR magnetic field with the EC, leading to a low product yield, so far demanded relatively long signal averaging. A critical assessment of what is and what is not (yet) possible with this approach is presented, for example in terms of structure elucidation and the estimation of concentrations. Additionally, promising routes for further improvement of EC-SPE-stripline-NMR are discussed.
authors.affiliation: AIMMS Division of BioMolecular Analysis, VU University Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Falck
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Oosthoek-de Vries
authors.forename: Ard
authors.initials: A
authors.lastname: Kolkman
authors.forename: Henk
authors.initials: H
authors.lastname: Lingeman
authors.forename: Maarten
authors.initials: M
authors.lastname: Honing
authors.forename: Sybren S
authors.initials: SS
authors.lastname: Wijmenga
authors.forename: Arno P M
authors.initials: AP
authors.lastname: Kentgens
authors.forename: Wilfried M A
authors.initials: WM
authors.lastname: Niessen
mesh_terms: D004563:Electrochemistry / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005240:Feasibility Studies; D017022:Flow Injection Analysis / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation*; D008904:Miniaturization; D048308:Mitogen-Activated Protein Kinase 14 / Q000032:analysis* / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000295:instrumentation*
chemical_list: D048308:Mitogen-Activated Protein Kinase 14